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Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders

Brain amyloid deposition is an early pathological event in Alzheimer’s disease (AD), and abnormally low levels amyloid-β(42) peptide (Aβ(42)) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ(42) decline among non-de...

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Autores principales: Dou, Kai-Xin, Zhang, Can, Tan, Chen-Chen, Xu, Wei, Li, Jie-Qiong, Cao, Xi-Peng, Tan, Lan, Yu, Jin-Tai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710044/
https://www.ncbi.nlm.nih.gov/pubmed/31370031
http://dx.doi.org/10.18632/aging.102125
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author Dou, Kai-Xin
Zhang, Can
Tan, Chen-Chen
Xu, Wei
Li, Jie-Qiong
Cao, Xi-Peng
Tan, Lan
Yu, Jin-Tai
author_facet Dou, Kai-Xin
Zhang, Can
Tan, Chen-Chen
Xu, Wei
Li, Jie-Qiong
Cao, Xi-Peng
Tan, Lan
Yu, Jin-Tai
author_sort Dou, Kai-Xin
collection PubMed
description Brain amyloid deposition is an early pathological event in Alzheimer’s disease (AD), and abnormally low levels amyloid-β(42) peptide (Aβ(42)) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ(42) decline among non-demented elders, we conducted a genome-wide association study involved 321 non-demented elders from Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1/GO/2 cohorts restricted to non-Hispanic Caucasians. A novel genome-wide significant association of higher annualized percent decline of CSF Aβ(42) in the gene CBFA2T3 (CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10(−9)) was identified. Besides displaying abnormal CSF Aβ(42) levels, rs13333659-T carriers were more likely to exhibit a greater longitudinal cognitive decline (p = 0.029, β = 0.097) and hippocampal atrophy (p = 0.029, β = −0.160) in the non-demented elders, especially for the participants who were amyloid-positive at baseline. These findings suggest rs13333659 in CBFA2T3 as a risk locus to modulate the decline rate of CSF Aβ(42) preceding the onset of clinical symptoms.
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spelling pubmed-67100442019-09-05 Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders Dou, Kai-Xin Zhang, Can Tan, Chen-Chen Xu, Wei Li, Jie-Qiong Cao, Xi-Peng Tan, Lan Yu, Jin-Tai Aging (Albany NY) Research Paper Brain amyloid deposition is an early pathological event in Alzheimer’s disease (AD), and abnormally low levels amyloid-β(42) peptide (Aβ(42)) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ(42) decline among non-demented elders, we conducted a genome-wide association study involved 321 non-demented elders from Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1/GO/2 cohorts restricted to non-Hispanic Caucasians. A novel genome-wide significant association of higher annualized percent decline of CSF Aβ(42) in the gene CBFA2T3 (CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10(−9)) was identified. Besides displaying abnormal CSF Aβ(42) levels, rs13333659-T carriers were more likely to exhibit a greater longitudinal cognitive decline (p = 0.029, β = 0.097) and hippocampal atrophy (p = 0.029, β = −0.160) in the non-demented elders, especially for the participants who were amyloid-positive at baseline. These findings suggest rs13333659 in CBFA2T3 as a risk locus to modulate the decline rate of CSF Aβ(42) preceding the onset of clinical symptoms. Impact Journals 2019-08-01 /pmc/articles/PMC6710044/ /pubmed/31370031 http://dx.doi.org/10.18632/aging.102125 Text en Copyright © 2019 Dou et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Dou, Kai-Xin
Zhang, Can
Tan, Chen-Chen
Xu, Wei
Li, Jie-Qiong
Cao, Xi-Peng
Tan, Lan
Yu, Jin-Tai
Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title_full Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title_fullStr Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title_full_unstemmed Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title_short Genome-wide association study identifies CBFA2T3 affecting the rate of CSF Aβ(42) decline in non-demented elders
title_sort genome-wide association study identifies cbfa2t3 affecting the rate of csf aβ(42) decline in non-demented elders
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710044/
https://www.ncbi.nlm.nih.gov/pubmed/31370031
http://dx.doi.org/10.18632/aging.102125
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